Abstract
Purpose
We evaluated the protective effect of PRP on ovarian function in female rats with cyclophosphamide (Cy)-induced ovarian damage.
Methods
Thirty-two adult female Sprague–Dawley rats were randomly divided into four groups. Group 1 (control-sodium chloride 0.9%; 1 mL/kg, single-dose ip injection), group 2 (Cy); 75 mg/kg, single-dose ip injection and sodium chloride 0.9% (1 mL/kg, single-dose ip injection), group 3 Cy plus PRP, Cy (75 mg/kg, single-dose and PRP (200 μl, single-dose) ip injection), group 4 (PRP, 200 μl, single-dose ip injection). Primordial, antral, and atretic follicle counts; serum anti-Müllerian hormone (AMH) levels; AMH-positive granulosa cells; and gene expression analysis of Ddx4 were assessed.
Results
Serum AMH levels were significantly lower in group 2 compared to groups 1, 3, and 4 (p < 0.01, p < 0.01, and p = 0.04, respectively). A significant difference was found in the primordial, primary, secondary, antral, and atretic follicle counts between all groups (p < 0.01). There was a statistically significant difference in AMH-positive staining primary, secondary, and antral follicles count between the groups (p < 0.01). There was a statistically significant difference in primary, secondary, and antral AMH positive staining follicle intensity score between the groups (p < 0.01). Ddx4 expression in group 4 was highest compared to other groups.
Conclusion
Our study may provide evidence that PRP could protect ovarian function against ovarian damage induced by Cy. It could lead to improved primordial, primary, secondary, and antral follicle numbers.
Similar content being viewed by others
References
Woad KJ, Watkins WJ, Prendergast D, Shelling AN. The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol. 2006;46:242–4.
Shelling AN. Premature ovarian failure. Reproduction. 2010;140:633–41.
Sheikhansari G, Aghebati-Maleki L, Nouri M, Jadidi-Niaragh F, Yousefi M. Current approaches for the treatment of premature ovarian failure with stem cell therapy. Biomed Pharmacother. 2018;102:254–62.
Sukur YE, Kivancli IB, Ozmen B. Ovarian aging and premature ovarian failure. J Turk-German Gynecol Assoc. 2014;15:190–6.
van Kasteren Y. Treatment concepts for premature ovarian failure. J Soc Gynecol Investig. 2001;8:58–S59.
Blumenfeld Z. Chemotherapy and fertility. Best Pract Res Clin Obstet Gynaecol. 2012;26(3):379–90.
Meirow D, Biederman H, Anderson RA, Wallace WH. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol. 2010;53:727–39.
Meirow D. Reproduction post-chemotherapy in young cancer patients. Mol Cell Endocrinol. 2000;169:123–31.
Soleimani R, Heytens E, Darzynkiewicz Z, Oktay K. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise. Aging. 2011;3(8):782–93.
Zhou L, Xie Y, Li S, Liang Y, Qiu Q, Lin H, et al. Rapamycin prevents cyclophosphamide-induced over-activation of primordial follicle pool through PI3K/Akt/mTOR signaling pathway in vivo. J Ovar Res. 2017;10(1):56.
Yuksel A, Bildik G, Senbabaoglu F, Akın N, Arvas M, Unal F, et al. The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells. Hum Reprod. 2015;30:2926–35.
Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85(6):638–46.
Pintat J, Silvestre A, Magalon G, Gadeau AP, Pesquer L, Perozziello A, et al. Intra-articular injection of mesenchymal stem cells and platelet-rich plasma to treat patellofemoral osteoarthritis: preliminary results of a long-term pilot study. J Vasc Interv Radiol. 2017;28(12):1708–13.
Lee KS, Wilson JJ, Rabago DP, Baer GS, Jacobson JA, Borrero CG. Musculoskeletal applications of platelet-rich plasma: fad or future? AJR Am J Roentgenol. 2011;196(3):628–36.
Bir SC, Esaki J, Marui A, Yamahara K, Tsubota H, Ikeda T, et al. Angiogenic properties of sustained release platelet-rich plasma: characterization in-vitro and in the ischemic hind limb of the mouse. J Vasc Surg. 2009;50(4):870–9 e2.
Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, et al. Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am. 2012;94(4):298–307.
Li W, Enomoto M, Ukegawa M, Hirai T, Sotome S, Wakabayashi Y, et al. Subcutaneous injections of platelet-rich plasma into skin flaps modulate proangiogenic gene expression and improve survival rates. Plast Reconstr Surg. 2012;129(4):858–66.
Bielecki TM, Gazdzik TS, Arendt J, Szczepanski T, Krol W, Wielkoszynski T. Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. J Bone Joint Surg Br Volüme. 2007;89(3):417–20.
Cieslik-Bielecka A, Bielecki T, Gazdzik TS, Arendt J, Krol W, Szczepanski T. Autologous platelets and leukocytes can improve healing of infected high-energy soft tissue injury. Transfusion Apheresis Sci: official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis. 2009;41(1):9–12.
Dehghani F, Aboutalebi H, Esmaeilpour T, Panjehshahin MR, Bordbar H. Effect of platelet-rich plasma (PRP) on ovarian structures in cyclophosphamide-induced ovarian failure in female rats: a stereological study. Toxicol Mech Methods. 2018;28(9):653–9.
Pedersen T, Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil. 1968;17:555–7.
Yeh J, Kim BS, Peresie J. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. Am J Obstet Gynecol. 2008;198(4):463.e1–6.
Christin-Maitre S, Braham R. General mechanisms of prematüre ovarian failure and clinical check-up. Gynecol Obstet Fertil. 2008;36:857–61.
Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Hum Reprod Update. 2012;18:525–35.
Hao X, Anastácio A, Liu K, Rodriguez-Wallberg KA. Ovarian follicle depletion induced by chemotherapy and the investigational stages of potential fertility-protective treatments-a review. Int J Mol Sci. 2019;23(19):20.
Ben-Aharon I, Meizner I, Granot T, Uri S, Hasky N, Rizel S, et al. Chemotherapy-induced ovarian failure as a prototype for acute vascular toxicity. Oncologist. 2012;17:1386–93.
Jayasinghe YL, Wallace WHB, Anderson RA. Ovarian function, fertility and reproductive lifespan in cancer patients. Expert Rev Endocrinol Metab. 2018;13:125–36.
Ronnes H, Kashi O, Meirow D. Prevention of chemotherapy-induced ovarian damage. Fertil Steril. 2016;105:20–9.
Kalich-Philosoph L, Roness H, Carmely A, Fishel-Bartal M, Ligumsky H, Paglin S, et al. Cyclophosphamide triggers follicle activation causing ovarian reserve ‘burn out’; AS101 prevents follicle loss and preserves fertility. Sci Transl Med. 2013;5:185ra62.
Bedoschi G, Navarro PA, Oktay K. Chemotherapy-induced damage to ovary: mechanisms and clinical impact. Future Oncol. 2016;12:2333–44.
Gonfloni S, Di Tella L, Caldarola S, Cannata SM, Klinger FG, Di Bartolomeo C, et al. Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nat Med. 2009;15:1179–85.
Ganesan S, Keating AF. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion. Toxicol Appl Pharmacol. 2016;292:65–74.
Leng L, Tan Y, Gong F, Hu L, Ouyang Q, Zhao Y, et al. Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency. Hum Reprod. 2015;30(3):737–48.
Bukovsky A. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases. Reprod Biol Endocrinol. 2015;13:10.
Fabi S, Sundaram H. The potential of topical and injectable growth factors and cytokines for skin rejuvenation. Facial Plast Surg. 2014;30:157–71.
Babu M, Wells A. Dermal-epidermal communication in wound healing. Wounds. 2001;13:183–9.
Herraiz S, Buigues A, Diaz-Garcia C, Romeu M, Martinez S, Gomez-Segui I, et al. Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion. Fertil Steril. 2018;109:908–18.
Huang Q, Liu B, Jiang R, Liao S, Wei Z, Bi Y, et al. G-CSF-mobilized peripheral blood mononuclear cells combined with platelet-rich plasma accelerate restoration of ovarian function in cyclophosphamide-induced POI rats. Biol Reprod. 2019;101:91–101.
Dehghani F, Sotoude N, Bordbar H, Panjeshahin MR, Karbalay-Doust S. The use of platelet-rich plasma (PRP) to improve structural impairment of rat testis induced by busulfan. Platelets. 2019;30(4):513–20.
Vural B, Duruksu G, Vural F, Gorguc M, Karaoz E. Effects of VEGF + mesenchymal stem cells and platelet-rich plasma on inbred rat ovarian functions in cyclophosphamide-induced premature ovarian insufficiency model. Stem Cell Rev. 2019;15(4):558–73.
Pantos K, Simopoulou M, Pantou A, Rapani A, Tsioulou P, Nitsos N, et al. A case series on natural conceptions resulting in ongoing pregnancies in menopausal and prematurely menopausal women following platelet-rich plasma treatment. Cell Transplant. 2019;4:963689719859539. https://doi.org/10.1177/0963689719859539.
Anderson RA, Fulton N, Cowan G, Coutts S, Saunders PT. Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis. BMC Dev Biol. 2007;7:136.
Guo K, Li CH, Wang XY, He DJ, Zheng P. Germ stem cells are active in postnatal mouse ovary under physiological conditions. Mol Hum Reprod. 2016;22(5):316–28.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ozcan, P., Takmaz, T., Tok, O.E. et al. The protective effect of platelet-rich plasma administrated on ovarian function in female rats with Cy-induced ovarian damage. J Assist Reprod Genet 37, 865–873 (2020). https://doi.org/10.1007/s10815-020-01689-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-020-01689-7